Abstract:
:Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. Orthotopic patient-derived pancreatic cancer xenografts treated biweekly with gemcitabine via the device for 7 weeks experienced a mean log2 fold change in tumor volume of -0.8 compared to a mean log2 fold change in tumor volume of 1.1 for intravenous (IV) gemcitabine, 3.0 for IV saline, and 2.6 for device saline groups. The weekly coadministration of systemic cisplatin therapy and transdermal device cisplatin therapy significantly increased tumor growth inhibition and doubled the survival in two aggressive orthotopic models of breast cancer. The addition of radiotherapy to this treatment further extended survival. Device delivery of gemcitabine in dogs resulted in more than 7-fold difference in local drug concentrations and 25-fold lower systemic drug levels than the IV treatment. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Byrne JD,Jajja MR,O'Neill AT,Bickford LR,Keeler AW,Hyder N,Wagner K,Deal A,Little RE,Moffitt RA,Stack C,Nelson M,Brooks CR,Lee W,Luft JC,Napier ME,Darr D,Anders CK,Stack R,Tepper JE,Wang AZ,Zamboni WC,Yeh JJ,doi
10.1126/scitranslmed.3009951subject
Has Abstractpub_date
2015-02-04 00:00:00pages
273ra14issue
273eissn
1946-6234issn
1946-6242pii
7/273/273ra14journal_volume
7pub_type
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